Day-Long Integrated Serum Insulin and C-Peptide Profiles in Patients With NIDDM: Correlation With Urinary C-Peptide Excretion

To determine whether non-insulin-dependent diabetes mellitus (NIDDM) is characterized by day-long hypoinsulinemia, we measured 24-h serum profiles for glucose, insulin, and C-peptide by use of a constant-rate blood-withdrawal technique in diabetic and control subjects fed isocaloric meals. When only lean subjects were considered, diabetic subjects (relative body weight 0.99 ± 0.3) and control subjects (relative body weight 0.95 ± 0.03) had similar 24-h integrated serum insulin concentrations (13.4 ± 2.5 vs. 16.1 ± 2.0 μU/ml, P NS) due to the offsetting effects of increased basal levels and decreased postprandial responses in NIDDM. In contrast, both basal and meal-stimulated insulin levels were decreased in obese NIDDM subjects (relative body weight 1.39 ± 0.07) compared with obese control subjects (relative body weight 1.60 ± 0.08), resulting in a 61% reduction in the 24-h integrated insulin value (18.7 ± 1.5 vs. 48.4 ± 13.7 μU/ml). Thus, the capacity to increase 24-h integrated serum insulin as a function of relative body weight was impaired in NIDDM subjects ( r = 0.27, P NS) compared with control subjects ( r = .70, P P P r = .69) and C-peptide ( r = .67) concentrations in control subjects but not in NIDDM subjects ( r = .20 and .04, respectively, P NS). Additionally, the urinary clearance of C-peptide was increased in NIDDM (38.1 ± 7.8 vs. 20.4 ± 1.7 ml/min in control subjects, P 1 ) lean but not obese untreated patients can have normal 24-h integrated serum insulin values due to the combination of high fasting and decreased postprandial levels, 2 ) 24-h integrated C-peptide values are decreased in both lean and obese patients, 3 ) intensive therapy normalizes 24-h integrated serum insulin but not C-peptide levels, and 4 ) urinary Cpeptide per se cannot be used as an index of insulin secretion because urinary C-peptide clearance is elevated and varies with treatment status.